This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in about 20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative. Following a genome scan in 53 kindreds in which 2 or more sibling were affected by age 65 with colon cancer, we performed finemapping on chromosomes 9 and 6 using densely spaced microsatellite markers. We further confirmed these signals in an additional 70 kindreds for which signal strength on chromosome 9 was increased by an order of magnitude. SNP typing in this region was completed and identification of a haplotype segregating preferentially in cases, and not controls, identified. We compiled a replication sample to confirm this association and collected additional family members so as to confirm this haplotype. A paper is in preparation that (1) confirmed the same linkage in a large dataset, narrowing the linkage region from 13-5 to 7.7 cm, (2) could further isolate this effect by a family-based assocation analysis of over 3,000 SNPs very densely spaced over the region of interest, and (3) identified a haplotype associated with risk of early onset familial colon neoplasia.